Meta analysis of efficacy and safety of a new oral anticoagulant after left atrial appendage closure
-
摘要: 目的 评估新型口服抗凝剂(NOAC)应用于左心耳封堵术(LAAC)后患者的疗效以及安全性。方法 计算机检索中国知网(CNKI)、维普(VIP)、万方、中国生物医学文献数据库(CMB)、Pubmed、Embase、Cochrane Library数据库，检索范围为2000年—2022年11月。检验漏斗图的对称性以评估纳入研究有无偏倚，应用Revman5.3合并RR值进行meta分析。结果 最终纳入12篇文献，其中前瞻性队列研究1篇和回顾性队列研究11篇，总计13 480例研究对象。Meta分析结果显示，与标准治疗方案相比，NOAC对围手术期不良事件减少相关(RR=0.39，95%CI 0.21~0.73，P < 0.05；I2=16%，P=0.31)，随访45 d内对器械相关血栓(DRT)事件(RR=0.68，95%CI 0.49~0.96，P=0.03；I2=0%，P=0.45)、大出血事件(RR=0.54，95%CI 0.39~0.75，P < 0.05；I2=0%，P=0.96)、所有出血事件(RR=0.27，95%CI 0.14~0.54，P < 0.05；I2=0%，P=0.49)、全因死亡事件(RR=0.55，95% CI 0.44~0.69，P < 0.05；I2=0.82，P=0.82)减少相关，与复合栓塞事件无统计学差异(RR=0.88，95%CI 0.221~3.49，P=0.86；I2=46%，P=0.10)，在平均随访期45~868 d内，与华法林相比，NOAC对复合栓塞事件(RR=0.60，95%CI 0.45~0.81，P < 0.05；I2=0%，P=0.45)、DRT事件(RR=0.68，95%CI 0.50~0.93，P=0.02；I2=26%，P=0.22)、大出血事件(RR=0.53，95%CI 0.44~0.64，P < 0.05；I2=0%，P=0.66)、所有出血事件(RR=0.45，95%CI 0.28~0.72，P < 0.05；I2=9%，P=0.36)、全因死亡事件(RR=0.51，95%CI 0.44~0.60，P < 0.05；I2=0%，P=1.00)减少相关，与残余漏(PDL)>5 mm(RR=0.75，95%CI 0.44~1.29，P=0.30；I2=0%，P=0.32)无统计学差异。讨论 NOAC在左心耳封堵术后的应用具有良好的疗效与安全性，对围手术期不良事件以及随访期内DRT形成、大出血、所有出血事件、全因死亡事件的发生优于华法林治疗。Abstract: Objective To evaluate the efficacy and safety of a new oral anticoagulant(NOAC) in patients after left atrial appendage occlusion(LAAC).Methods The computer searches CNKI, VIP, Wanfang, China Biomedical Literature Database(CMB), Pubmed, Embase, and Cochrane Library databases from 2000 to November 2022. The symmetry of funnel chart was tested to assess whether the included studies were biased. Revman 5.3 was used to combine RR values for Meta-analysis.Results 12 articles were finally included, including 1 prospective cohort study and 11 retrospective cohort studies, with a total of 13, 480 subjects. Meta analysis results showed that compared with the standard treatment regimen, NOAC was associated with the reduction of adverse events during perioperative period(RR=0.39, 95%CI 0.21-0.73, P < 0.05, I2=16%, P=0.31). During the 45 days of follow-up, NOAC was associated with the reduction of DRT events(RR=0.68, 95%CI 0.49-0.96, P=0.03, I2=0%, P=0.45), massive bleeding events(RR=0.54, 95%CI 0.39-0.75, P < 0.05, I2=0%, P=0.96), all bleeding events(RR=0.27, 95%CI 0.14-0.54, P < 0.05, I2=0%, P=0.49) The reduction of all-cause death events(RR=0.55, 95%CI 0.44-0.69, P < 0.05, I2=0.82, P=0.82) was related to the reduction of composite embolic events, and there was no statistical difference with composite embolic events(RR=0.88, 95%CI 0.221-3.49, P=0.86, I2=46%, P=0.10). During the average follow-up period of 45 days to 868, compared with warfarin, NOAC was associated with composite embolic events(RR=0.60, 95%CI 0.45-0.81, P < 0.05, I2=0%, P=0.45), DRT events(RR=0.68, 95%CI 0.50-0.93, P=0.02, I2=26%, P=0.22), massive hemorrhage events(RR=0.53, 95%CI 0.44-0.64, P < 0.05, I2=0%, P=0.66) The reduction of all bleeding events(RR=0.45, 95%CI 0.28-0.72, P < 0.05, I2=9%, P=0.36) and all-cause death events(RR=0.51, 95%CI 0.44-0.60, P < 0.05, I2=0%, P=1.00) was related to the reduction of residual leakage(PDL)>5 mm. (RR=0.75, 95%CI 0.44-1.29, P=0.30, I2=0%, P=0.32)Conclusion The application of NOAC after left atrial appendage closure has good efficacy and safety, and is superior to warfarin in the treatment of adverse events in the perioperative period and the occurrence of DRT formation, massive hemorrhage, all bleeding events, and all cause death events during the follow-up period.
-
Key words:
- atrial fibrillation /
- left atrial appendage closure /
- novel oral anticoagulant /
- warfarin
-
-
图 5 平均随访期疗效指标森林图
Figure 5. Forest map of efficacy index during average follow-up period
图 6 平均随访期安全性指标森林图
Figure 6. Forest map of safety index during average follow-up period
表 1 纳入文献的研究特征
Table 1. Research characteristics of the included literatures
纳入研究 国家 研究类型 封堵器 NOAC组治疗方案 华法林组治疗方案 第1次TEE/CTA NOAC样本量/例 华法林样本量/例 随访时间 卢2022[10] 中国 队列研究(单中心前瞻性) NA NOAC 3个月，后3个月双抗，终身口服单抗 华法林3个月，后3个月双抗，终身口服单抗 3个月 152 103 6个月 Freeman 2022[11] 美国 队列研究(多中心回顾性) Watchman NOAC 45 d，后4.5个月双抗，终身口服单抗 华法林45 d，后4.5个月双抗，终身口服单抗 45 d 6 649 4 330 6个月 Ge 2022[12] 中国 队列研究(单中心回顾性) Watchman NOAC 45 d，后4.5个月双抗，终身口服单抗 华法林45 d，后4.5个月双抗，终身口服单抗 6周 38 46 1年 Ajmal 2022[13] 美国 队列研究(单中心回顾性) Watchman NOAC 45 d，后4.5个月双抗，终身口服单抗 华法林45 d，后4.5个月双抗，终身口服单抗 45 d 57 152 23.5个月 Chen 2021[14] 中国 队列研究(单中心回顾性) Watchman(86.1%)，Amplatze(13.9%) NOAC 45 d，后4.5个月双抗，终身口服单抗 华法林45 d，后4.5个月双抗，终身口服单抗 45 d 170 170 868 d Fu 2022[15] 中国 队列研究(单中心回顾性) Watchman NOAC至少45 d，后4.5个月双抗 华法林至少45 d，后4.5个月双抗 45 d 291 77 45 d Zhu 2021[16] 中国 队列研究(单中心回顾性) Watchman NOAC 45 d，后4.5个月双抗，终身口服单抗 华法林45 d，后4.5个月双抗，终身口服单抗 45 d 40 30 45 d Fry 2021[17] 美国 队列研究(多中心回顾性) Watchman NOAC 45 d，后4.5个月双抗，终身口服单抗 华法林45 d，后4.5个月双抗，终身口服单抗 45 d 69 89 1年 Cohen 2019[18] 美国 队列研究(单中心回顾性) Watchman NOAC 6周，之后4.5个月双抗，终身口服单抗 华法林6周，后4.5个月双抗，终身口服单抗 6周 47 43 8个月 傅2019[19] 中国 队列研究(单中心回顾性) Watchman NOAC 45 d，后4.5个月双抗，终身口服单抗 华法林45 d，后4.5个月双抗，终身口服单抗 45 d 152 60 6个月 陈2018[20] 中国 队列研究(单中心回顾性) Watchman(91.5%)，Amplatzer(8.5%) NOAC 45 d，后4.5个月双抗，终身口服单抗 华法林45 d，后4.5个月双抗，终身口服单抗 45 d 29 160 45 d Enomoto 2017[21] 美国 队列研究(多中心回顾性) Watchman NOAC服用6周 华法林服用6周 6周(60%)，4个月(40%) 214 212 4个月 
下载: 导出CSV
表 2 纳入研究基线特征表
Table 2. Baseline characteristics in study included
纳入研究 年龄/岁 男性/% CHA2DS2-VASc/分 HAS-BLED/分 阵发性房颤/% 持续性房颤/% 卢2022 69.2/68.7 61.8/ 68.0 3.4/3.6 2.7/3.0 NR NR Freeman 2022 75.9/76.0 54.9/54.9 4.5/4.5 2.8/2.9 51.0/49.4 24.4/21.0 Ge 2022 66.1/69.8 71.1/58.7 3.8/4.1 2.7/2.7 26.4/23.9 73.6/76.1 Ajmal 2022 75.3/74.3 56.0/58.0 4.0/4.0 4.0/4.0 29.8/52.6 70.2/47.4 Chen 2021 65.6/64.1 59.4/62.9 3.3/2.9 1.9/1.7 2.9/0 97.1/100 Fu 2022 69.6/69.8 65.6/69.8 4.5/4.5 3.0/3.1 17.0/16.9 83.0/83.1 Zhu 2021 67.0/ 65.0 52.5/66.7 4.0/3.0 3.2/3.2 NR NR Fry 2021 80.0 42.3 5.0 2.6 NR NR Cohen 2019 76.9/76.8 67.3/57.8 4.7/4.7 3.5/3.5 44.2/28.9 55.8/71.1 傅2019 69.6/70.3 57.9/60.0 4.8/4.3 3.1/3.1 32.9/31.7 67.1/68.3 陈2018 64.0/65.0 58.6/63.1 3.0/2.8 2.3/1.7 NR NR Enomoto 2017 76.0/75.0 63.0/69.0 3.8/4.1 2.4/2.7 NR NR 纳入研究 心力衰竭/% 糖尿病/% 高血压/% 脑梗死/TIA/血栓栓塞/% 出血史/% 肾功能不全/% 卢2022 NR 27.0/20.4 71.1/ 75.7 58.6/53.4 9.2/12.6 NR Freeman 2022 32.4/38.9 34.3/37.8 91.7/91.2 NR 68.0/70.3 11.8/13.7 Ge 2022 NR 15.8/17.4 76.8/63.0 55.3/45.7 NR 2.6/4.3 Ajmal 2022 17.5/25.0 31.6/29.6 14.0/22.4 14.0/22.4 NR 0/10.5 Chen 2021 17.1/20.0 16.5/15.9 66.5/62.9 44.1/41.2 NR NR Fu 2022 11.1/11.1 37.8/13.0 70.1/66.2 62.5/75.0 19.8/23.4 NR Zhu 2021 7.5/3.3 25.0/13.3 60.0/80.0 77.5/73.3 12.5/13.3 7.5/16.7 Fry 2021 45.4 41.8 92.0 27.6 NR NR Cohen 2019 25.0/48.9 23.1/20.0 88.5/91.1 51.9/48.9 NR NR 傅2019 13.3/11.7 16.4/16.7 64.4/61.7 81.6/78.3 25.0/26.7 NR 陈2018 20.7/16.9 34.5/15.6 72.4/ 63.1 37.9/40.6 NR NR Enomoto 2017 NR NR NR NR NR NR 注：数据以NOAC/华法林的形式呈现，其中Fry以整个样本量水平报告；NR：未报告。
下载: 导出CSV
表 3 NOAC组服药情况表
Table 3. Situation in NOAC group
% 纳入研究 阿哌沙班 利伐沙班 达比加群 艾多沙班 卢2022 0 NR NR 0 Freeman 2022 NR NR NR NR Ge 2022 0 0 100 0 Ajmal 2022 49.1 40.4 7.0 3.5 Chen 2021 NR NR NR NR Fu 2022 0 43.3 56.7 0 Zhu 2021 0 60.0 40.0 0 Fry 2021 72.5 18.8 8.7 0 Cohen 2019 87.2 8.5 4.3 0 傅2019 0 61.8 38.2 0 陈2018 0 NR NR 0 Enomoto 2017 46 46 7 1 注：NR：未报告。
下载: 导出CSV
表 4 亚组分析结果
Table 4. Results of subgroup analysis
研究项目 亚组 合并后RR(95%CI) I2 亚组间异质性 围手术期不良事件 样本量均衡组 0.53(0.20~1.34) 0% 0% 样本量不均衡组 0.30(0.13~0.67) 53% 随访45 d复合血栓事件 样本量均衡组 3.49(0.39~31.16) 0% 41% 样本量不均衡组 0.55(0.10~3.09) 53% 随访期DRT事件 样本量均衡组 1.11(0.38~3.21) 0% 0% 样本量不均衡组 0.65(0.47~0.90) 47%
下载: 导出CSV
-
[1] 马建帅, 何长健, 袁明, 等. 非瓣膜性心房颤动左心耳血栓状态与纤维蛋白原的相关性[J]. 临床心血管病杂志, 2021, 37(9): 796-801. doi: 10.13201/j.issn.1001-1439.2021.09.004
[2] Infeld MM, Silverman DN, Lustgarten DL. Left atrial appendage closure: a safe and effective alternative to anticoagulation?[J]. J Innovat Cardiac Rhythm Manage, 2019, 10(1): 3486-3493. doi: 10.19102/icrm.2019.100107
[3] Holmes DR, Reddy VY, Turi ZG, et al. Percutaneous closure of the left atrial appendage versus warfarin therapy for prevention of stroke in patients with atrial fibrillation: a randomised non-inferiority trial[J]. Lancet, 2009, 374(9689): 534-542. doi: 10.1016/S0140-6736(09)61343-X
[4] Holmes DR, Kar S, Price MJ, et al. Prospective randomized evaluation of the Watchman Left Atrial Appendage Closure device in patients with atrial fibrillation versus long-term warfarin therapy: the PREVAIL trial[J]. JACC, 2014, 64(1): 1-12. doi: 10.1016/j.jacc.2014.04.029
[5] Birkinshaw A, Fry CH, Fluck D, et al. Changing trends in the use of novel oral anticoagulants and warfarin for treating non-valvular atrial fibrillation[J]. JRSM Cardiovasc Dis, 2020, 9: 2048004020915406. http://pubmed.ncbi.nlm.nih.gov/32284860/
[6] 唐亮, 胡豫. 新型口服抗凝剂在肿瘤相关静脉血栓栓塞症治疗中的应用[J]. 临床血液学杂志, 2019, 32(1): 1-5. https://www.cnki.com.cn/Article/CJFDTOTAL-LCXZ201901001.htm
[7] Iskandar S, Vacek J, Lavu M, et al. Left atrial appendage closure for stroke prevention: devices, techniques, and efficacy[J]. Cardiology Clinics, 2016, 34(2): 329-351. doi: 10.1016/j.ccl.2015.12.009
[8] 陈敏, 陈慧, 林玮玮, 等. 非瓣膜性心房颤动患者利伐沙班群体药代动力学研究[J]. 临床心血管病杂志, 2020, 36(8): 724-730. https://www.cnki.com.cn/Article/CJFDTOTAL-LCXB202008010.htm
[9] Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses[J]. Eur J Epidemiol, 2010, 25(9): 603-605. doi: 10.1007/s10654-010-9491-z
[10] 卢艳钦, 李晓烨, 张晓春, 等. 非瓣膜性心房颤动患者左心耳封堵术后新型口服抗凝药治疗的疗效与安全性[J]. 中国新药与临床杂志, 2022, 41(9): 543-548. https://www.cnki.com.cn/Article/CJFDTOTAL-XYYL202209007.htm
[11] Freeman JV, Higgins AY, Wang Y, et al. Antithrombotic therapy after left atrial appendage occlusion in patients with atrial fibrillation[J]. JACC, 2022, 79(18): 1785-1798. doi: 10.1016/j.jacc.2022.02.047
[12] Ge H, Zhang C, Qiao Z Q, et al. Risk of device-related thrombosis following short-term oral anticoagulation with low-dose dabigatran versus warfarin after Watchman left atrial appendage occlusion[J]. Sci progress-uk, 2022, 105(3): 368504221113194.
[13] Ajmal M, Hutchinson MD, Lee K, et al. Outcomes in patients implanted with a Watchman device in relation to choice of anticoagulation and indication for implant[J]. J Interv Card Electr, 2022, 64(1): 1-8. doi: 10.1007/s10840-021-00958-4
[14] Chen Y, Zhang Y, Qu L, et al. Short-term non-vitamin K antagonist oral anticoagulants vs. warfarin in preventing device-related thrombosis after left atrial appendage closure[J]. J Thromb Thrombolys, 2021, 52(3): 872-879. doi: 10.1007/s11239-021-02408-4
[15] Fu G, Wang B, He B, et al. Safety and efficacy of low-dose non-vitamin K antagonist oral anticoagulants versus warfarin after left atrial appendage closure with the Watchman device[J]. J Formos Med Association, 2022, 121(8): 1488-1494. doi: 10.1016/j.jfma.2021.10.015
[16] Zhu J, Xu J. The use of novel non-vitamin k antagonist oral anticoagulants following closure of the left atrial appendage: preliminary results of clinical follow-up[J]. Drug Design Develop Therapy, 2021, 15: 1067-1073. doi: 10.2147/DDDT.S293812
[17] Fry E, Bollempali H, Suarez K, et al. Watchman outcomes comparing post-implantation anticoagulation with warfarin versus direct oral anticoagulants[J]. J Interv Card Electr, 2021, 61(1): 137-144. doi: 10.1007/s10840-020-00790-2
[18] Cohen JA, Heist EK, Galvin J, et al. A comparison of postprocedural anticoagulation in high-risk patients undergoing WATCHMAN device implantation[J]. Pace, 2019, 42(10): 1304-1309. http://pubmed.ncbi.nlm.nih.gov/31479160/
[19] 傅国华, 王彬浩, 何斌, 等. 经皮植入左心耳封堵器后不同抗凝药物应用的安全性及有效性观察[J]. 中华心律失常学杂志, 2019, 10(6): 530-534.
[20] 陈雨意, 陈艳红, 张勇华, 等. 新型口服抗凝药物用于经皮左心耳封堵术术中、术后抗凝的初步临床随访结果[J]. 中国介入心脏病学杂志, 2018, 26(10): 547-552. https://www.cnki.com.cn/Article/CJFDTOTAL-ZJXB201810007.htm
[21] Enomoto Y, Gadiyaram VK, Gianni C, et al. Use of non-warfarin oral anticoagulants instead of warfarin during left atrial appendage closure with the Watchman device[J]. Heart rhythm, 2017, 14(1): 19-24. http://www.sciencedirect.com/science/article/pii/S1547527116309389
[22] Giorgini P, Di Giosia P, Grassi D, et al. Air Pollution exposure and blood pressure: an updated review of the literature[J]. Curr pharm design, 2016, 22(1): 28-51. http://www.onacademic.com/detail/journal_1000040520478410_c8ac.html
[23] 赵薇, 何红, 代静, 等. 不同制备量的去白混合浓缩血小板质量指标分析[J]. 临床血液学杂志, 2022, 35(2): 134-137. https://www.cnki.com.cn/Article/CJFDTOTAL-LCXZ202202012.htm
[24] 王子卿, 胡晓梅, 李芋锦, 等. 阿司匹林抵抗的真性红细胞增多症及原发性血小板增多症患者临床特征及凝血状态分析[J]. 临床血液学杂志, 2021, 34(11): 790-794. https://www.cnki.com.cn/Article/CJFDTOTAL-LCXZ202111009.htm
[25] Li W, Gao R F, Zhao J, et al. Safety and efficacy of different anticoagulation regimens after left atrial appendage occlusion[J]. Annals of Palliative Medicine, 2022, 11(1): 201-9.
[26] Liu XX, Kleinecke C, Busch S, et al. Propensity-matched comparison of antiplatelet versus anticoagulant after left atrial appendage closure with the Watchman[J]. Pace Pacing Clin Electrophysiol, 2020, 43(11): 1242-1251. http://pubmed.ncbi.nlm.nih.gov/32779203/
[27] Zhang ZH, Yao Q, Huang HY, et al. Efficacy and safety of dabigatran and dual antiplatelet therapy after left atrial appendage occlusion with the Watchman device[J]. Int J Clin Expe Med, 2018, 11(9): 9819-9826.
[28] Beyer-Westendorf J, Ehlken B, Evers T. Real-world persistence and adherence to oral anticoagulation for stroke risk reduction in patients with atrial fibrillation[J]. Europace, 2016, 18(8): 1150-1157. http://www.ncbi.nlm.nih.gov/pubmed/26830891
-
图(6)
表(4)
计量
- 文章访问数: 1979
- PDF下载数: 332
- 施引文献: 0